Blood circulation disorder occurred by the blockage of blood flow caused by deposited cholesterol and increased thrombus on blood vessel, and lessened elastic force of blood vessel. The representative symptoms of blood circulation disorder are benumbed feet or hand, crick of neck and shoulders, loss of memory, lethargy, loss of concentration, vertigo and chronic fatigue etc., which often give difficulty in normal living life. Hyperlipemia, as one example of blood circulation disorder, is a condition where the blood lipid parameters are elevated in the blood. This condition manifests an abnormally high concentration of fats in the blood. The lipid component in the circulating blood is total cholesterol, low density lipoproteins, very low density lipoproteins or triglycerides.
Inflammation occurred by the invasion of outer contaminant, for example, bacteria, fungus, virus, various allergens inducing inflammatory response and a biophysical process against them. The characteristic syndrome of inflammatory response is serial and complex physiological response such as the enhancement of enzyme activity, the release of inflammatory mediators, fluidal infiltration, cell movement, tissue disruption together with external syndromes such as erythema, edema, pyrexia, ache and so on.
NO (nitric oxide), a factor of those inflammatory responses is formed by NOS (nitric oxide synthase), which acts on L-arginine to form final products, i.e., NO and citrulline through an intermediate (hydroxyarginine). The substance has small molecular weight and it has been found that it acts on blood vessel system to induce vasodilation, platelet agglutination and adhesion, neuronal transmission, gastrointestinal movement and plays a important roles in controlling metabolic pathway and physiological reaction such as neuronal transmission, blood coagulation, blood pressure regulation and the immunity against cancer cell etc. It is highly toxic because of its free radical structure and is prone to be changed to stabilized final product i.e., NO3 and NO2 in the air (Snyder S. H., et al, Scientific American, May pp 28-35, 1992).
NOS can be classified with cNOS (constitutive NOS) and iNOS (inducible NOS) according to the dependence to calcium ion or calmodulin; wherein cNOS dependent to calcium ion or calmodulin is present mainly in brain, epithelial cell, neutrophil, stomach mucous cell and; wherein iNOS independent to calcium ion or calmodulin is present mainly in macrophage, hepatic cell, cancer cell etc and is induced by several factors, for example, cytokines such as IL-1beta, IFN-gamma, TNF-alpha, or an endotoxin such as bacterial LPS (Dinerman, J. L., et al, Circ. Res., 73, pp 217-222, 1993). iNOS expression is closely correlated with COX-2 expression, therefore, formed NO may affects on COX-2 expression (Robert C., et al., J. Immunol., 165, pp 1582-1587, 2000; Daniela S., et al., Proc. Nat'l. Acad. Sci. USA, 90, pp 7240-7244, 1993).
Additionally, there have been many reports on the correlation between NO production caused by iNOS and various inflammatory diseases such as atheriosclerosis, arthritis, gastritis, colitis, nephritis, hepatitis, cancer or various degenerative diseases (Gobert A. P. et al., J. Immunol. 168(12), pp 6002-6006, 2002; Dijkstra G. et al., Scand. J. Gastroenterol., 37(5) pp 546-554, 2002; Sakac V. and Sakac M. Med. Pregl., 53, pp 463-474, 2000; Albrecht E. W. et al., Am. J. Transplant, 29(5), pp 448-453, 2002; Ramachandran A. et al., Free Radical Biol. Med., 33(11) pp 1465-1474, 2002; Sartor L. et al., Biochemical Pharmacol., 64, pp 229-237, 2002; Sadowska Krowicka H. et al., Proc. Soc. Exp. Biol. Med., 217(3), pp 351-357 1998; Lo A. H. et al., Carcinogenesis, 23(6) pp 983-991, 2002)
Accordingly, there have been investigated to develop a medicine, health care food or food additives to treat and prevent above described various inflammatory diseases by finding potent inhibitors for the production of NO caused by iNOS.
Bamboo belonged to Bambusaceae or Poaceae is distributed in Asian countries including Korea and Japan. There are about 1259 species of bamboo all over the world. Among them, the representative ones belonged to Bambusaceae are Phyllostachys bambusoides SIEB. Et Zucc, Phyllostachys nigra MUNRO, Phyllostachys nigra MUNRO var. henonis STAPF and Phyllostachys pubescens MAZEL ex H. de LEH, and the representative ones belonged to another Poaceae are Sasa borealis Makino, Sasa coreana Nakai, Sasa japonica Makino, Sasa borealis var. gracilis, Sasa palmata Nakai, Setaria viridis BEAUV and Oryza sativa L.
There have been several reports on the use of bamboo extract, for example, Korean Patent Publication No. 10-2001-69130 discloses on the process for preparing the leave extract from Sasa japonica Makino and the use of the same as a food preservative using its antimicrobial activity; U.S. Pat. No. 3,418,311 discloses the polysaccharide isolated from bamboo having anticancer activity.
However, there has been not reported or disclosed about therapeutic effect for inflammatory or blood circulation disease of bamboo extract and the compound isolated therefrom in any of above cited literatures, the disclosures of which are incorporated herein by reference.
To investigate and confirm the treating or preventing effect on inflammatory or blood circulation disease of bamboo extract and the compound isolated therefrom through several biochemical experiments, the inventors of the present invention have intensively carried out several biological experiments i.e., in vitro inhibition test on NO or PLA2 production induced by LPS activated macrophage and an effects on the expression of several gene such as u-PA, eNOS and VEGF known to play an important role in thrombolytic activity, the control of blood flow and the cell growth in blood vessel together with cytotoxicity test, as well as animal model test using LDL receptor defected mouse and normal mouse and finally completed present invention by confirming that the extract and the compound isolated therefrom have the treating and preventing activity on inflammatory or blood circulation diseases.
These and other objects of the present invention will become apparent from the detailed disclosure of the present invention provided hereinafter.